Investigation of Nickel Sensitization After Percutaneous Implantation of Patent Foramen Ovale Occluder

NCT ID: NCT04713683

Last Updated: 2025-02-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 96 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-10
• Study Completion Date: 2024-12-01

Brief Summary

Percutaneous PFO closure has been established as a first-line therapy for preventing recurrent strokes in selected patients. The devices used for the specific purpose contain and release nickel, which is considered as the most allergen metal in nature. Skin patch tests are considered as gold-standard for documenting nickel allergy. While the allergic contact dermatitis induced by nickel is well described, literature is inadequate on explaining the effect of nickel release on the clinical manifestations of patients implanted with such devices.

Our prospective, randomized, blinded trial will try to investigate the above by performing nickel skin patch tests to all patients, 14 days before and 90 days after the implantation. During follow-up, clinical manifestations and transthoracic echocardiographic findings will be evaluated and associated with patch skin tests.

Detailed Description

Percutaneous PFO closure has been established as a first-line therapy for preventing recurrent strokes, after embolic stroke of unknown source (ESUS) and a patent foramen ovale. The PFO closure is achieved by the implantation of suitable devices, which occlude the shunt between the two atria and prevent the creation and detachment of thrombi. Until today, there are two devices approved by FDA for the specific purpose; Amplatzer PFO Occluder and Gore Cardioform Septal Occluder. Despite the architectonic differences between these devices, the main material of both is nitinol, an alloy of nickel and titanium. While titanium is an extremely rare allergen, nickel is considered as one of the most common allergens and the most frequent metal allergen in nature, with a prevalence about 20%. The main clinical expression of nickel hypersensitivity is allergic contact dermatitis, but cases with systemic allergic reaction have been described as well. It has been observed that nickel is released by the implanted devices and circulates through bloodstream, having the potential to cause systemic clinical picture. Device syndrome includes signs and symptoms (i.e. palpitations, dyspnea, chest pain, rash, etc.), which are appeared after the device placement and are associated with hypersensitivity reaction. The existing literature is considered as inadequate for explaining the effect of nickel release in the patients implanted with an occluder.

The aim of our study is to evaluate whether patients with nickel hypersensitivity have an increased risk of adverse events following PFO closure, to assess the potential influence of device selection, and to evaluate potential sensitization or desensitization in patients without or with pre-existing nickel allergy, respectively.

Nickel hypersensitivity was assessed using skin patch testing prior to the procedure. The primary endpoint was device syndrome, a composite of patient-reported symptoms (chest pain, palpitations, migraines, dyspnea, and rash). Secondary endpoints included arrhythmias, bleeding, stroke, and all-cause mortality.

Conditions

Foramen Ovale, Patent; Nickel Sensitivity; Dermatitis Contact Irritant; Metal Allergy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Amplatzer PFO Occluder

Patients randomized in this arm will be implanted with Amplatzer PFO Occluder.

Group Type: ACTIVE_COMPARATOR

Percutaneous Patent Foramen Ovale Closure

Intervention Type: DEVICE

Patients with well-documented embolic stroke of unknown source (ESUS) and a patent foramen ovale (PFO) are indicated for percutaneous closure of PFO. The intervention is performed through the right femoral vein. The interventional cardiologist introduces the sheath and advances the device via inferior vena cava to right atrium. Then, the catheter is passed through the PFO, the device is deployed and the occlusion is achieved. The procedure is performed under fluoroscopy guidance with or without transesophageal echocardiography guidance.

Gore Cardioform Septal

Patients randomized in this arm will be implanted with Gore Cardioform Septal Occluder.

Group Type: ACTIVE_COMPARATOR

Percutaneous Patent Foramen Ovale Closure

Intervention Type: DEVICE

Patients with well-documented embolic stroke of unknown source (ESUS) and a patent foramen ovale (PFO) are indicated for percutaneous closure of PFO. The intervention is performed through the right femoral vein. The interventional cardiologist introduces the sheath and advances the device via inferior vena cava to right atrium. Then, the catheter is passed through the PFO, the device is deployed and the occlusion is achieved. The procedure is performed under fluoroscopy guidance with or without transesophageal echocardiography guidance.

Interventions

Percutaneous Patent Foramen Ovale Closure

Patients with well-documented embolic stroke of unknown source (ESUS) and a patent foramen ovale (PFO) are indicated for percutaneous closure of PFO. The intervention is performed through the right femoral vein. The interventional cardiologist introduces the sheath and advances the device via inferior vena cava to right atrium. Then, the catheter is passed through the PFO, the device is deployed and the occlusion is achieved. The procedure is performed under fluoroscopy guidance with or without transesophageal echocardiography guidance.

Intervention Type: DEVICE

Other Intervention Names

Transcatheter PFO occlusion

Eligibility Criteria

Inclusion Criteria

• Age: at least 14 years old
• Well-documented indication for percutaneous PFO closure

Exclusion Criteria

• Corticosteroid treatment
• Patient's refusal to participation

• Minimum Eligible Age: 14 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National and Kapodistrian University of Athens

OTHER

Sponsor Role: lead

Responsible Party

Konstantinos Toutouzas

Professor of Cardiology, First Department of Cardiology, Medical School

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Konstantinos Toutouzas, MD,PhD

Role: STUDY_CHAIR

First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

Anastasios Apostolos, MD

Role: PRINCIPAL_INVESTIGATOR

First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

Stamatios Gregoriou, MD, PhD

Role: STUDY_DIRECTOR

First Department of Dermatology-Venereolgy, National and Kapodistrian University of Athens, Andreas Syggros Hospital

Locations

First Department of Cardiology, National and Kapodistrian University of Athens, Hippokration General Hospital of Athens

Athens, Attica, Greece

Countries

Greece

References

Apostolos A, Drakopoulou M, Toutouzas K. New migraines after atrial septal defect occlusion. Is the nickel hypersensitivity the start of everything? Med Hypotheses. 2021 Jan;146:110442. doi: 10.1016/j.mehy.2020.110442. Epub 2020 Nov 30. No abstract available.

Reference Type: RESULT

PMID: 33303305 (View on PubMed)

Ahlstrom MG, Thyssen JP, Wennervaldt M, Menne T, Johansen JD. Nickel allergy and allergic contact dermatitis: A clinical review of immunology, epidemiology, exposure, and treatment. Contact Dermatitis. 2019 Oct;81(4):227-241. doi: 10.1111/cod.13327. Epub 2019 Jul 9.

Reference Type: RESULT

PMID: 31140194 (View on PubMed)

Schalock PC, Crawford G, Nedorost S, Scheinman PL, Atwater AR, Mowad C, Brod B, Ehrlich A, Watsky KL, Sasseville D, Silvestri D, Worobec SM, Elliott JF, Honari G, Powell DL, Taylor J, DeKoven J. Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society. Dermatitis. 2016 Sep-Oct;27(5):241-7. doi: 10.1097/DER.0000000000000210.

Reference Type: RESULT

PMID: 27649347 (View on PubMed)

Prestipino F, Pragliola C, Lusini M, Chello M. Nickel allergy induced systemic reaction to an intracardiac amplatzer device. J Card Surg. 2014 May;29(3):349-50. doi: 10.1111/jocs.12331.

Reference Type: RESULT

PMID: 24762035 (View on PubMed)

Apostolos A, Gregoriou S, Drakopoulou M, Trantalis G, Tsiogka A, Ktenopoulos N, Aggeli K, Stratigos A, Tsioufis K, Toutouzas K. Patent Foramen Ovale Closure in Patients With and Without Nickel Hypersensitivity: A Randomized Trial. Circ Cardiovasc Interv. 2025 Apr;18(4):e015228. doi: 10.1161/CIRCINTERVENTIONS.125.015228. Epub 2025 Mar 9.

Reference Type: DERIVED

PMID: 40057986 (View on PubMed)

Other Identifiers

NICKEL-PFO TRIAL

Identifier Type: -

Identifier Source: org_study_id